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Biomarqueurs du syndrome coronarien aigu

Biomarqueurs du syndrome coronarien aigu. JP Cristol, S Badiou, AS Bargnoux, N Kuster, AM Dupuy. Biomarkers associated with various pathophysiological processes of acute coronary syndromes. Risk Factors For cardiovascular disease:. Myocardial Infarction Biomarkers. cTnI / TnT. Necrosis.

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Biomarqueurs du syndrome coronarien aigu

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  1. Biomarqueurs du syndrome coronarien aigu JP Cristol, S Badiou, AS Bargnoux, N Kuster, AM Dupuy.

  2. Biomarkers associated with various pathophysiological processes of acute coronary syndromes. Risk Factors For cardiovascular disease: Myocardial Infarction Biomarkers cTnI / TnT Necrosis CKMB Leucocytes Activation MPO Metalloproteinase H-FABP Biomarkers of ACS AVP Axis activation Copeptin CRP , Il-6 sPLA2 … Inflammation BNP NT-pro-BNP ANP Biomechanical stress Endothelial Activation/ Dysfunction Adrenomedullin Endothelin Chan and Ng BMC Medicine 2010, 8:34

  3. De l’occlusion partielle vers l’occlusion totale Thrombus Plaque fissurée

  4. De l’occlusion partielle vers l’occlusion totale : Du SCA vers l’IDM ST+ • Artère coronaire non complètement occluse • Risque évolutif à court terme vers SCA ST+ ou mort subite SCA ST+ cTn élevée SCA ST - Cinétique cTn ? Normale ou élevée

  5. Stratifier le risque : Scores clinico-biologiques : Score de TIMI Risque de mortalité ou de complications graves (Antman EM, The TIMI risk score for unstable angina/non-ST elevation MI, JAMA 2000 ; 284: 835-842) (http://www.mdcalc.com/uanstemitimiscore)

  6. Classification des syndromes coronariens aigus Angor stable SCA non ST + SCA ST + Angor Instable : Pas d’élévation de cTn NSTEMI : IDM non ST+ IDM sans onde Q cTn positive STEMI : IDM ST+ cTn positive Désobstruction en urgence Nécessite cinétique de cTn ou nouveaux marqueurs D’après «A consensus document of The Joint European Society of Cardiology / American College of Cardiology. Eur. Heart J., 2000; 21:1502-13.

  7. ST + = extrême urgence médicale (H6) Occlusion coronaire Désobstruction !! (Angioplastie, thrombolyse) SCA ST+ Un sus-décalage du segment ST dans 2 dérivations contiguës d’un territoire coronaire d’au moins 0,1 mV dans les dérivations frontales (D1, D2, D3, aVL, aVF), précordiales gauches (V4, V5, V6) ou postérieures (V7, V8, V9) d’au moins 0,2 mV dans les dérivations droites (V1, V2, V3) ECG

  8. Efficacité de la désobstruction Angioplastie (The GUSTO Angiographic Investigators. The effects of tissue plasminogen acti-vator, streptokinase, or both on coronary-artery patency, ventricular function andsurvival after acute myocardial infarction. N Engl J Med 1993; 329: 1615-1622)

  9. Pas de ST + Signes électriques atypiques ou ECG normal ECG

  10. USA en 2004 > 1million de SCA non ST+ recensés (European Heart Journal 2007) La fréquence de l’IDM alors que SCA non ST+ 1/3 des DT répond aux critères diagnostics de SCA non ST+ L’évolution à long terme est moins favorable que SCA ST+ ? (European Heart Journal 2007) Epidémiologie comparée des SCA ST + et ST -

  11. Pronostic à long terme Mortalité hospitalière des SCA non ST+ < ST+ Mortalité à 6 mois idem et > à long terme (Keth AA Fox, BMJ, Prediction of risk of death and myocardial infarction in the 6 months after presentation ACS, prospective multinational observational study (GRACE))

  12. Clef de voûte de la PEC Clinique et ECG insuffisante Marqueurs biologiques, incontournables Stratification du risque SCA ST+ cTn élevée Pas de marqueurs SCA ST - Cinétique cTn Biomarqueurs

  13. Biomarqueurs et infarctus cTnrise cTnfall

  14. Spécificité CK-LDH-Myoglobine CK-MB cTnI ou T + ++ +++ Classification

  15. En discussion lors d’une suspicion d’un 2éme IDM pour évaluer la taille de l’IDM en présence d’une IRC Suspicion de faux positifs de la cTn National Academy of Clinical Biochemistry (NACB) en 2007 dosage justifié si cTn non disponible La place de la CK-MB actuellement

  16. H-FABP ou heart-type fatty acid-binding protein protéine liée aux acides gras soluble de 132 acides aminés proche de la myoglobine Les limites cardiospécificité limitée, étroitesse de la fenêtre diagnostique (20 à 30 h) élimination rénale quasi exclusive Dosage réactif Randox immunoturbidimétrique sur Cobas 2936 publications entre 1979-2011 La h-FABP

  17. La h-FABP

  18. La h-FABP

  19. The combination of H-FABP and Tnincreased the NPV Mc Mahon 2011

  20. Troponins : the corner stone of the Universal definition of myocardial infarction ESC Guidelines for the management of acute myocardialinfarction. European Heart Journal, 2012

  21. The spectrum of acute coronary syndromes : STEMI – NSTEMI – Unstableangina Hamm, et al., Eur Heart J. 2011 Dec;32(23):2999-3054

  22. No early change in cTn Kinetic studies with troponins :six hours to detect myocardial infarction Myocadial infarction cTnrise cTnfall

  23. TROPONINES • TnIc et TnTc sont des composant des myocytes • Libérées dans le sang lors de la lésion des cellules myocardiques: ischémie, nécrose , inflammation, traumatisme, toxique • Spécificité et sensibilité ++++ • Aucun intérêt dans les 2 à 3 premières heures de la douleur • augmente 4 à 6h après le début de la symptomatologie • (2ème dosage à réaliser entre 6-12h si 1er négatif

  24. Roche TnT The goal for sensitive troponins :diagnosis of AMI as early as possible. Roche TnT 718 Pts with acute chest pain Tn levels at baseline Diagnostic accuracy of Tn at presentation according to time since onset of chest pain Reichlin et al. NEJM 2009

  25. Need for a Universally Accepted Nomenclature • Defining Uniform Criteria for Reference Populations • Analytical Imprecision in Cardiac Troponin Assays • Ruling in / Ruling Out Acute myocardial infarction : • Elevated but stable hs-Tn and risk stratification Emergence of TNT : Important issues for hs-Tn. Frederick K. Korley and Allan S. Jaffe, J Am CollCardiol 2013;61:1753–8

  26. Un passeport pour les troponines - Quelle signification : Un marqueur de SCA ? Un marqueur pronostic ? Un marqueur de remodelage ?- Quelle troponine ? T ou I ? Apple FS (2009) Clin Chem, 55(7):1303 1396

  27. Troponine assays classified as « guideline acceptable »

  28. Une troponine “positive” :quelle signification ? • Critèresd’interprétation : • Le 99° percentile (14 ng/L pour hs-TnT) • La valeur du delta en cinétique Seuil clinique ?

  29. Need for a Universally Accepted Nomenclature • Defining Uniform Criteria for Reference Populations • Analytical Imprecision in Cardiac Troponin Assays • Ruling in / Ruling Out Acute myocardial infarction : • Elevated but stable hs-Tn and risk stratification Emergence of TNT : Important issues for hs-Tn. Frederick K. Korley and Allan S. Jaffe, J Am CollCardiol 2013;61:1753–8

  30. Relationship Between age and the 99% URL in Healthy Individuals Venge 2009

  31. Age-dependent TnT percentiles in Emergencing Room patients. 651 patients 205 > 65 446 < 65 Ola Hammarsten et al., Clinical Chemistry 58:3 (2012)

  32. Le 99° percentile etles facteurs de risque cardiovasculaire p<0.001 p=n.s. p=n.s. p=0.017 10 8 6 cTnT-hs (ng/L) 4 2 0 (-) (-) (-) (-) (+) (+) (+) (+) (-) (-) (-) (-) (+) (+) (+) (+) Diabetesmellitus Hypertension Dyslipidemia Obesity 10 p=0.043 p=0.004 p<0.001 p=n.s. 8 6 cTnT-hs (ng/L) 4 2 0 Currentsmoking Family historyof CVD LVH CKD Otsuka T. et al., Am Heart J, 159(6): 972–8, 2010

  33. How to select a reference population ? * Young individuals or age-matched patients ? recommendation of a 2n foldapproach in whichbothyounger (< 30 YO) and older (> 30 YO; median 60 to berepresentative of the ages of cardiac patients) * Apparentlyhealthy questionnaire screening, eGFR, ECG, cardiacimaging * adequatenumber of individuals : 300 – 500 individuals * Shouldbedone for each test The Upper Reference Limitand the 99th percentile…. Apple FS, Collinson PO Clin Chem 2012;58; 58:54–61.

  34. Relationship Between Patient Characteristics and the 99% URL in Healthy Individuals Frederick K. Korley and Allan S. Jaffe, J Am CollCardiol 2013;61:1753–8

  35. Le 99° Percentile dans la populaton agée …. En fonction des ATCD cardiaques n=591 n=375

  36. eGFR and the 99° Percentile in elderly n=253 n=122 Stage 3a : 82 Stage 3b : 30 Stage 4 : 7 Stage 5 : 3 At the Emergency departement : 51% hs-cTnT > 14 ng/L (cTnI > 40 ng/L – 18%)

  37. The 99° Percentile in the elderly Kuster et al., submitted

  38. Emergence of TNT : Important issues for hs-Tn. • Need for a Universally Accepted Nomenclature • Defining Uniform Criteria for Reference Populations • Analytical Imprecision in Cardiac Troponin Assays • Ruling in / Ruling Out Acute myocardial infarction : • Elevated but stable hs-Tn and risk stratification Frederick K. Korley and Allan S. Jaffe, J Am CollCardiol 2013;61:1753–8

  39. Great attention should be paid to analytical Imprecision in Cardiac Troponin Assays • Avoiding classical interference • Autoantibodies to cTnI or cTnT are found in 5% to 20% of individuals and can reduce detection of cTn • Anticoagulant interferences • Avoiding lot-to-lot variations

  40. Implications of Adjustment of High-Sensitivity Cardiac Troponin Assay Kuster et al., Clinical Chemistry 59:3 (2013)

  41. Need for a Universally Accepted Nomenclature • Defining Uniform Criteria for Reference Populations • Analytical Imprecision in Cardiac Troponin Assays • Ruling in / Ruling Out Acute myocardial infarction : • Rule out by undetectable hs-Tn at presentation ? • Kinetic studies remain necessary to rule in … • Very short, short or long kinetic studies? • What is the optimal delta change ? • 5) Elevated but stable hs-Tn and risk stratification Emergence of TNT : Important issues for hs-Tn. Frederick K. Korley and Allan S. Jaffe, J Am CollCardiol 2013;61:1753–8

  42. Rapid rule out of acute myocardial infarction using undetectable levels of hs- troponin at admission 2072 consecutive patients Maria Rubini Giménez et al. International Journal of Cardiology xxx (2013) xxx–xxx

  43. Rapid rule out of acute myocardial infarction using undetectable levels of hs- troponin Stratification by time from onset Maria Rubini Giménez et al. International Journal of Cardiology xxx (2013) xxx–xxx

  44. Accelerated diagnostic protocol (ADP) for excluding major adverse cardiovascular events (MACE) using clinic data and hs-cTnI ADAPT cohort : patients with at least 5 min of possible cardiac symptoms APACE cohort : patients presented to the emergency departments in a multinational, multicenter study with symptoms suggestive of AMI hs-TnI at 0 and 2 h < 26.2 ng/l. Cullen et al. JACC Vol. 62, No. 14, 2013

  45. Short kinetic studies should be used with caution An interesting finding in this study was that a conservative estimate of the 1st percentile of cTnT in NSTEMI patients remained below 12 ng/L until 8.5 h after onset of symptoms, and 6 h after arrival at the ER. Ola Hammarsten et al., Clinical Chemistry 58:3 (2012)

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